Ascorbic acid, also known as vitamin C, is an essential vitamin in the human body, which cannot synthesize vitamin C on its own. Although widely recognized for its role in the human immune system, ascorbic acid is also essential to other functions, such as the synthesis of collagen. Ascorbic acid's benefits are largely attributable to its ability to act as a reducing agent. Thus, ascorbic acid is able to boost the immune system by scavenging harmful free radicals, which are highly reactive molecular fragments having one or more unpaired electrons. [N. Sax & R. Lewis Sr., Hawley's Condensed Chemical Dictionary, 11th ed. Van Nostrand Reinhold 1987]. These free radicals are typically generated by the production or transfer of energy; thus, organs that use, or are exposed to, a great deal of energy, such as the brain and skin, generate numerous free radicals. For example, the transfer of energy from ultraviolet light to the skin generates free radicals such as singlet oxygen, superoxide anions, and hydroxyl radicals. [U.S. Pat. No. 5,574,063, Col. 1, lines 33-46]. If unchecked, these free radicals steal ions from other molecules, thereby destroying cells and tissues and causing chain reactions that oxidize lipids, DNA and enzymes. This often results in physical manifestations, such as sunburn and premature aging. [Id. at Col. 1, lines 40-50]. At high concentrations, ascorbic acid can protect the body against free radicals by donating ions to the free radicals, thereby neutralizing them. Moreover, ascorbic acid can help regenerate the reduced form of Vitamin E, .alpha.-tocopherol, thereby rejuvenating another one of the body's major antioxidants. [H. Padh, Vitamin C: Newer Insights into its Biochemical Functions, Nutr. Rev. 49:65-70 (1991)].
Additionally, ascorbic acid acts as an enzyme or coenzyme in several of the body's internal chemical processes by reducing various chemical components in the process. In particular, ascorbic acid is essential to the formation of collagen, the key structural component of the extracellular network that gives strength and resilience to bodily tissues. Collagen consists of three helices spiraled around each other and bound together by hydrogen bonds, which individually are weak but collectively impart a structural strength greater than steel upon the collagen. The hydrogen bonds are catalyzed through the action of two enzymes, hydroxylase and lysyl oxidase, which are activated by ascorbic acid. Without ascorbic acid, the hydrogen bonds will not form and the collagen will fall apart, which results in a deterioration of the structural fabric of the skin, wrinkles, and in extreme cases resulting in scurvy. Ascorbic acid is not only essential to the body's production of collagen, but in the production of epinephrin, bile acid and steroids as well. [Murray et al., Harper's Biochemistry Twenty-Fourth Edition, Appleton & Lange, pgs. 612-613. (1996)].
Unfortunately, the same attributes that make ascorbic acid vital to the human body also make it susceptible to rapid degradation, thereby making it difficult to formulate stable pharmaceutical compositions with therapeutically effective amounts of ascorbic acid. The rapid degradation of ascorbic acid is largely due to: stereochemical strains created by polar repulsive forces, oxidative degradation due to the propensity of ascorbate anions to act as a reductant, and degradation due to bulk water attack. [U.S. Pat. No. 5,140,043, Col. 2, lines 24-47].
Previously, efforts were made to overcome these difficulties by using low weight ascorbic acid, nonaqueous solvents, or derivatives of ascorbic acid. All of these methods limit the bioavailability of ascorbic acid and therefore limit the effectiveness of the formulation.
In particular, U.S. Pat. No. 5,140,043 discloses allegedly stable ascorbic acid compositions. These compositions consist of aqueous solutions containing a concentration of L-ascorbic acid above 1% W/V and having a pH below 3.5. The acidic pH of the topical application could irritate the user's skin, making the application less desirable.
Thus, a need exists for non-irritating, stable pharmaceutical compositions of ascorbic acid, which may also be used for the prevention or treatment of skin damage caused by the harmful effects of free radicals.